Dopamine receptor-dependence of the amphetamine induction of the immediate-early genec-fos.
Item
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Title
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Dopamine receptor-dependence of the amphetamine induction of the immediate-early genec-fos.
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Identifier
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AAI9720099
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identifier
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9720099
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Creator
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Jaeger, David Alex.
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Contributor
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Adviser: Stuart Sealfon
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Health Sciences, Pharmacology
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Abstract
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Amphetamine is a psychostimulant whose behavioral effects have been directly attributed to increased subcortical dopaminergic neurotransmission. The goal of this thesis was to identify the relationship between signal transduction in neuronal pathways subserving the behavioral effects of amphetamine and dopamine receptor activation. This was accomplished by administering dopamine receptor-selective antagonists prior to treatment with amphetamine, and measuring the effects these drugs have on the induction of the immediate early gene c-fos in the striatum and primary motor cortex. Fos represents a signal transduction mechanism which has previously been shown to play a direct role in the locomotor effects of amphetamine. Positive Fos-immunolabeling of digitized images was determined utilizing an algorithm for selection of intensity thresholds, as this method was determined to be as accurate and more precise than subjective assessments.;D1-like dopamine receptor antagonism was less effective in reducing the amphetamine induction of c-fos in the primary motor cortex than D2-like dopamine receptor antagonism, despite the ability of D1-like dopamine receptor antagonism to eliminate the amphetamine induction of c-fos in the striatum. We suggest that the induction of c-fos in layer V pyramidal neurons of the primary motor cortex, like the striatum, is dependent upon dopamine receptor activation. The pattern of dopamine receptor-dependent gene induction likely reflects dopamine-receptor specific modulation of pathways communicating with the motor cortex. These studies contribute to an understanding of the molecular mechanisms through which dopaminergic neurotransmission, particularly that which is produced by the administration of drugs of abuse such as amphetamine, influences the neuronal circuits which subserve locomotion.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.